Epilepsy is a paroxysmal, self-sustaining and self-limiting cerebral dysrhythmia characterized by an abnormal and excessive EEG (electroencephalograph) discharge and by a disturbance of consciousness. During an episode of epileptic seizure, there may be involuntary body movement or hyperactivity of the autonomic nervous system. Different kinds of epileptic seizures can display various clinical phenomena and EEG activities. Such variations in clinical phenomena and EEG activities form the basis of the characterization of seizures.
In tonic-clonic seizures (grand mal), a seizure is characterized by a sequence of tonic spasms of body musculature followed by clonic jerking movement. Tonic spasm is characterized by continuous tension whereas clonic movement refers to alternate muscular contraction and relaxation in rapid succession. In status epilepticus, a succession of grand mal seizures take place without intervening return of consciousness to the individual. See Remington's Pharmaceutical Sciences, Mack Publishing Co., Ch. 56, pp. 1057-1066 and pp. 1072-1081, 18th ed., 1990, which is incorporated by reference.
Generally, it is desirable to prevent epileptic seizures in humans by maintaining effective drug therapy. However, if seizure takes place, particularly for seizures with extensive tonic-clonic duration, such as status epilepticus, it may be necessary to give prompt treatment to inhibit or moderate the seizure in order to prevent injury to the patient, such as bruises, cuts, broken arms or even damage caused by anoxia. Anti-epileptic drugs (i.e., drugs that inhibit epileptic seizure, either before or after the onset of epileptic seizure) can be given intravenously for acute inhibition of the epileptic seizure. See "Drugs for Epilepsy", The Medical Letter, Vol. 31, Issue 783, 1-4, 1989. However, in situations in which there is involuntarily convulsive movement, intravenous administration of drugs is not desirable because the patient's uncontrolled movement may hinder injection or even cause injuries. Moreover, intravenous injection of diazepam, a preferred anti-epileptic drug, is sometimes painful and can cause thrombophlebitis, an inflammation of a vein associated with thrombus formation. See Selander et al., Acta Anaesth. Scand., 25, 516-518 (1981).
A number of drugs are useful as anti-epileptic agents. See Remington's Pharmaceutical Sciences, supra. A convenient way to administer an anti-epileptic drug such as benzodiazepine, e.g. diazepam, is by ingestion so that the drug can be absorbed by the gastro-intestinal tract. Sheth et al. (U.S. Pat. No. 4,126,672) describe a sustained-release capsule for oral administration of diazepam. The capsules contain medicaments in combination with a hydrocolloid. Upon contact with gastric fluid, the hydrocolloid hydrates, forming an outside barrier which substantially retains the shape of the capsule. The hydrated layer slowly dissolves, releasing the medicament.
Fish et al. (U.S. Pat. No. 4,322,440) describe anti-convulsive compositions and methods of administering such compositions. The compositions are described as capable of being administered orally, as well as parenterally, i.e. via subcutaneous, intramuscular and intravenous injection. Fish et al. also disclose that the anti-convulsive compositions may be administered in the form of a rectal suppository. The suppository may be prepared by incorporating an active anti-convulsive agent into a shapable base material. Suitable suppository bases are described to include cocoa butter, glycerinated gelatin, hydrogenated vegetable oils, mixtures of polyethylene glucose, and fatty acid esters of polyethylene glycol.
However, for a patient having jerking movement because of seizure, the above-mentioned routes of drug administration are not practical. Intravenous injection of anti-epileptic agents is difficult. Oral administration is also impractical if the patient has no voluntary control of skeletal muscles. Rectal suppositories are slow-acting and therefore not effective for rendering fast relief of seizure. Therefore, there is a need for an epileptic-seizure-inhibiting composition that can be administered and absorbed quickly and safely.